Skip to main content
SpringerLink
Log in

Epstein-Barr virus-encoded latent membrane protein 1 modulates cyclin D1 by c-Jun/Jun B heterodimers

  • Published:
Science in China Series C: Life Sciences Aims and scope Submit manuscript

Abstract

In our recent studies, we found that LMP1 encoded by Epstein-Barr virus could accelerate the formation of active c-Jun/Jun B heterodimer. We studied the regulation of cyclinD1 by c-Jun/Jun B heterodimers by laser scanning confocal influorescence microscopy, Western blot, luciferase activity assay, super-EMSA and flow cytometry in the Tet-on-LMP1 HNE2 cell line, in which LMP1 expression was regulated by Tet-on system. c-Jun/Jun B heterodimers induced by LMP1 could up regulate cyclin D1 promoter activity and expression. Overexpression of cyclinD1 accelerated the progression of cell cycle.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Song, X., Tao, Y. G., Tan, Y. N. et al., Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein Barr virus encoded latent membrane protein 1, Science in China, Ser. C, 2005, 48(1): 70–80.

    Article  CAS  Google Scholar 

  2. Herber, B., Truss, M., Beato, M. et al., Inducible regulatory elements in the human cyclin D1 promoter, Oncogene, 1994, 9: 2105–2107.

    PubMed  CAS  Google Scholar 

  3. Bakiri, L., Lallemand, D., Ella, B. W. et al., Cell cycle-dependent variations in c-Jun and JunB phosphorylation: A role in the control of cyclin D1 expression, EMBO J., 2000, 19: 2056–2068.

    Article  PubMed  CAS  Google Scholar 

  4. Li, Z. K., Xie, L., He, Z. W. et al., Comparing the genes expression difference in nasopgaryngeal carcinoma with normal adult nosophorynx tissue by cDNA expression array, Chinese Science Bulletin, 1998, 43(22): 2462–2463.

    Google Scholar 

  5. Xie, L., Xun, L. G., He, Z. W. et al., Application of the differential hybridization of tumor cDNA arrays technique in the identification of expressed genes in the nasopharyngeal carcinoma, Progress in Natural Science (in Chinese), 2000, 10: 378–382.

    Google Scholar 

  6. Xiao, H., Gu, K. H., Cao, Y. et al., Study on differential cyclin D expression and cyclin D1gene amplification in the nasopharyngeal carcinoma, Zhonghua Er Bi Hou ke Za Zhi (in Chinese), 2000, 35: 2.

    Google Scholar 

  7. Song, X., Zhao, X. Y., Wang, Y. et al., Tissue microarray analysis of cyclinD1 gene overexpression in the multistage carcinogenesis of nasopharyngeal carcinoma, Prog. Biochem. Biophys. (in Chinese), 2002, 29: 385–389.

    CAS  Google Scholar 

  8. Liao, W., Tang, M., Deng, X. Y. et al., Epstein-Barr virus encoded latent membrane protein 1 promotes nuclear factor-kappa B activity in a nasopharyngeal carcinoma cell line, Chinese Journal of Virology (in Chinese), 2000, 16: 198–202.

    CAS  Google Scholar 

  9. Luo, F. J., Hu, Z., Zeng, L. et al., Experimental study on transcriptional regulation of malignant progression in nasopharyngeal carcinoma by EPSTEIN-BARR virus encoded latent membrane protein 1, Progress in Biochemistry and Biophysics (in Chinese), 2002, 29:567–571.

    CAS  Google Scholar 

  10. Zhao, X. R., Deng, L., Weng, X. X. et al., Further study on cyclin D1 expression and runction and function in human nasopharyngeal carcinoma cell line, Chin. J. Oncol. (in Chinese), 2001, 23: 373–375.

    CAS  Google Scholar 

  11. Zhao, X. R., Wang, C. X., Luo, F. J. et al., The Epstein-Barr virus encoded latent membrane protein 1 (EBV-LMP1) activates expression of cyclinD1, Progress in Biochemistry and Biophysics (in Chinese), 2001, 28: 704–710.

    Google Scholar 

  12. Zhao, X. R., Gu, H. H., Weng, X. X. et al., The primary study on expression and function of D-Type cyclin in nasopharyngeal carcinoma cell lines, Acta Biochimica et Biophysica Sinica (in Chinese), 2000, 32: 192–196.

    CAS  Google Scholar 

  13. Liao, W., Yi, H., Li, X. Y. et al., Doxycycline dependent expression of EBV latent membrane protein 1 with Tet regulating system in Nasopharygeal Carcinoma Cell Line, Acta Biochimica et Biophysica Sinica (Shanghai), 1999, 31: 309–312.

    CAS  Google Scholar 

  14. Sambrook, J., Fritsch, E. F., Maniatis, T., Molecular Cloning: A Laboratory Manual, 2nd ed., 1989, New York: Cold Spring Harbor Laboratory Press.

    Google Scholar 

  15. Andrews, N. C., Faller, D. V., A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells, Nucleic Acids Research, 1991, 19:2499.

    Article  PubMed  CAS  Google Scholar 

  16. Hinz, M., Krappmann, D., Eichten, A. et al., NF-κB function in growth control: Regulation of cyclinD 1 expression and G0/G1-to-S-phase transition, MCB, 1999, 19:2690–2698.

    PubMed  CAS  Google Scholar 

  17. Chapman, N. R., Perkins, N. D., Inhibition of the RelA(p65) NF-kappaB subunit by Egr-1, J. Biol. Chem., 2000, 275: 4719–4725.

    Article  PubMed  CAS  Google Scholar 

  18. Lee, W., Mitchell, P., Tjian, R., Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements, Cell, 1987, 49: 741–752.

    Article  PubMed  CAS  Google Scholar 

  19. Briggs, M. R., Kadonaga, J. T., Bell, S. P. et al., Purification and biochemical characterization of the promoter-specific transcription factor, Sp1, Science, 1986, 234:47–52.

    CAS  Google Scholar 

  20. Vallone, D., Battista, S., Pierantoni, G. M. et al., Neoplastic transformation of rat thyroid cells requires the JunB and fra-1 gene induction which is dependent on the HMGI-C gene product, EMBO J., 1997, 16:5310–5321.

    Article  PubMed  CAS  Google Scholar 

  21. Hu, Z., Zheng, L., Tao, Y. G. et al., EB virus-encoded latent membrane protein 1 activates the JNK signaling pathway via a mechanism involving TRADD and TRAF in nasopharyngeal carcinoma cell, Prog. Biochem. Biophys. (in Chinese), 2002, 29: 562–566.

    CAS  Google Scholar 

  22. Luo, F. J., Peng, X. N., Li, X. Y. et al., Epstain-Barr virus LMP1 up regulates activity of AP-1 in nasopharyngeal cell line, Chinese Journal of Biochemistry and Molecular Biology (in Chinese), 2000, 16:551–555.

    CAS  Google Scholar 

  23. Luo, F. J., Hu, Z., Cao, Y. et al., Epstain-Barr virus LMP1 up regulates activity of AP-1 through JNK passway in nasopharyngeal cell line, Chinese Journal of Biochemistry and Molecular Biology (in Chinese), 2001, 18: 114–119.

    Google Scholar 

  24. Molinari, M., Cell cycle checkpoints and their inactivation in human cancer, Cell Prolif., 2000, 33:261–274.

    Article  PubMed  CAS  Google Scholar 

  25. Sherr, J., Cancer cell cycle, Science, 1996, 274: 1672–1677.

    Article  PubMed  CAS  Google Scholar 

  26. Hunter, T., Pines, J., Cyclins and cancer (II): Cyclin D and CDK inhibitors come of age, Cell, 1994, 79: 573–582.

    Article  PubMed  CAS  Google Scholar 

  27. Arber, N., Hibshoosh, H., Moss, S. F. et al., Increased expression of Cyclin D1 is an early event in multistagecolorectal carcinogenesis, Gastroenterology, 1996, 110: 669–674.

    Article  PubMed  CAS  Google Scholar 

  28. Donjerkovic, D., Scott, D. W., Regulation of the G1 phase of the mammalian cell cycle, Cell Res., 2000, 10(1): 1–16.

    Article  PubMed  CAS  Google Scholar 

  29. Bartek, J., Lukas, J., Bartkova, J., Perspective: Defects in cell cycle control and cancer, J. Pathol., 1999, 187: 95–99.

    Article  PubMed  CAS  Google Scholar 

  30. Petty, W. J., Dragnev, K. H., Dmitrovsky, E., Cyclin D1 as a target for chemoprevention, Lung Cancer, 2003, Suppl 1: S155–161.

    Google Scholar 

  31. Zhu, G., Conner, S. E., Zhou, X. et al., Synthesis, structure-activity relationship, and biological studies of indolocarbazoles as potent cyclin D1-CDK4 inhibitors, J. Med. Chem., 2003, 46:2027–2030.

    Article  PubMed  CAS  Google Scholar 

  32. Engler, T. A., Furness, K., Malhotra, S. et al., Novel, potent and selective cyclinD1/CDK4inhibitors: Indolo[6,7-a]pyrrolo[3,4-c] carbazoles, Bioorg. Med. Chem. Lett., 2003, 13: 2261–2267.

    Article  PubMed  CAS  Google Scholar 

  33. Sharpless, T., Traganos, F., Darzynkiewicz, Z. et al., Flow cytofluorimetry: Discrimination between single cells and cell aggregates by direct size measurements, Acta Cytol., 1975, 19: 577–581.

    PubMed  CAS  Google Scholar 

  34. Tam, S. W., Theodoras, A. M., Shay, J. W. et al., Differential expression and regulation of cyclin D1 protein in normal and tumor human cells: Association with Cdk4 is required for cyclin D1 function in G1 progression, Oncogene, 1994, 9: 2663–2674.

    PubMed  CAS  Google Scholar 

  35. Nelsen, C. J., Rickheim, D. G., Timchenko, N. A. et al., Transient expression of cyclin D1 is sufficient to promote hepatocyte replication and liver growth in vivo, Cancer Res., 2001, 61: 8564–8568.

    PubMed  CAS  Google Scholar 

  36. Song, X., Cao, Y., Regulation of G1/S phase checkpoint and multistep carcinogenesis, Foreign Medical Science (Molecular Biology Section), 2002, 24: 73–76.

    Google Scholar 

  37. Robles, A. I., Larcher, F., Whalin, R. B. et al., Expression of cyclin D1 in epithelial tissues of transgenic mice results in epidermal hyperproliferation and severe thymic hyperplasia, Proc. Natl. Acad. Sci. USA, 1996, 93: 7634–7638.

    Article  PubMed  CAS  Google Scholar 

  38. Zhou, B. B., Elledge, S. J., The DNA damage response: Putting checkpoints in perspective, Nature, 2000, 408: 433–439.

    Article  PubMed  CAS  Google Scholar 

  39. Hu, Z., Tao, Y. G., Yang, L. F. et al., Effect of JIP on the proliferation and apoptosis of nasopharyngeal carcinoma cells, Ai Zheng (in Chinese), 2002, 21: 1182–1186.

    Google Scholar 

  40. Hu, Z., Tao, Y.G., Tang, F. Q. et al., Effect of JIP on the proliferation and apoptosis of nasopharyngeal carcinoma cells through interaction with JNK mediated pathway, Prog. Biochem. Biophys. (in Chinese), 30: 579–585.

  41. Deng, L., Yang, J., Cao, Y. et al., Cells in G2/M phase increased in human nasopharyngeal carcinoma cell line by EBV-LMP1 through activation of NF-κB and AP-1, Cell Res., 2003, 13: 187–194.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Research Institute, Xiangya School of Medicine, Central South University, 410078, Changsha, China

    Xin Song, Yongguang Tao, Liang Zeng, Jing Yang, Faqing Tang & Ya Cao

  2. Laboratory of Molecular Technology SAIC-Frederick, National Cancer Institute, P.O. Box B, 21702, Frederick, MD, USA

    Leo M. Lee

  3. Molecular Medical Center, Tongji Hospital, Tongji Medical University, 430030, Wuhan, China

    Jianping Gong

  4. Key Laboratory of the Ministry of Education for Cell Biology, and Tumor Cell Engineering, School of Life Sciences, Xiamen University, 361005, Xiamen, China

    Qiao Wu

Authors
  1. Xin Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongguang Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liang Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Faqing Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Leo M. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jianping Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qiao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ya Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ya Cao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, X., Tao, Y., Zeng, L. et al. Epstein-Barr virus-encoded latent membrane protein 1 modulates cyclin D1 by c-Jun/Jun B heterodimers. Sci. China Ser. C.-Life Sci. 48, 385–393 (2005). https://doi.org/10.1360/03yc0251

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1360/03yc0251

Keywords

Search

Navigation